TY - JOUR
T1 - Dihydropyrimidine dehydrogenase deficiency, a pharmacogenetic syndrome associated with potentially life-threatening toxicity following 5-fluorouracil administration
AU - Ezzeldin, Hany
AU - Diasio, Robert
PY - 2004/9
Y1 - 2004/9
N2 - Dihydropyrimidine dehydrogenase (DPD) deficiency is a pharmacogenetic syndrome associated with potentially life-threatening toxicity following the administration of standard doses of 5-fluorouracil.This syndrome derives its importance from the fact that approximately 2 million patients receive the drug worldwide each year. Population studies have suggested that 4%-7% of the American population exhibit dose-limiting toxicity that might be associated with a genetic defect in the DPYD gene that encodes for the DPD enzyme. During the past several years it has become increasingly clear that genetics is a major determinant of the variability in drug response, accounting for the probability of drug efficacy and the likelihood of toxic drug reactions.This article briefly discusses the clinical presentation, laboratory diagnosis, pharmacokinetics, inheritance, and the clinical management options of DPD deficiency. The variability of DPD enzyme activity in population studies and the different DPYD alleles together with new phenotypic and genotypic methods of screening for DPD deficiency will also be reviewed.
AB - Dihydropyrimidine dehydrogenase (DPD) deficiency is a pharmacogenetic syndrome associated with potentially life-threatening toxicity following the administration of standard doses of 5-fluorouracil.This syndrome derives its importance from the fact that approximately 2 million patients receive the drug worldwide each year. Population studies have suggested that 4%-7% of the American population exhibit dose-limiting toxicity that might be associated with a genetic defect in the DPYD gene that encodes for the DPD enzyme. During the past several years it has become increasingly clear that genetics is a major determinant of the variability in drug response, accounting for the probability of drug efficacy and the likelihood of toxic drug reactions.This article briefly discusses the clinical presentation, laboratory diagnosis, pharmacokinetics, inheritance, and the clinical management options of DPD deficiency. The variability of DPD enzyme activity in population studies and the different DPYD alleles together with new phenotypic and genotypic methods of screening for DPD deficiency will also be reviewed.
KW - Adverse drug reactions
KW - DPYD gene
KW - Pharmacogenomics
UR - http://www.scopus.com/inward/record.url?scp=16544376696&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=16544376696&partnerID=8YFLogxK
U2 - 10.3816/CCC.2004.n.018
DO - 10.3816/CCC.2004.n.018
M3 - Review article
C2 - 15377401
AN - SCOPUS:16544376696
SN - 1533-0028
VL - 4
SP - 181
EP - 189
JO - Clinical colorectal cancer
JF - Clinical colorectal cancer
IS - 3
ER -